scholarly journals Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Katherine T Best ◽  
Antonion Korcari ◽  
Keshia E Mora ◽  
Anne EC Nichols ◽  
Samantha N Muscat ◽  
...  
Keyword(s):  
Tendon Repair ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Cell Depletion ◽  
Cytoskeletal Organization ◽  
Cell Localization ◽  
Fundamental Understanding ◽  
Injury And Repair ◽  
Fibril Diameter

Despite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of ScxLin cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTR mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLin cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

scholarly journals Scleraxis-Lineage Cell Depletion Improves Tendon Healing and Disrupts Adult Tendon Homeostasis

2020 ◽  
Author(s):  
Katherine T. Best ◽  
Antonion Korcari ◽  
Keshia E. Mora ◽  
Emma Knapp ◽  
Mark R. Buckley ◽  
...  
Keyword(s):  
Tendon Repair ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Cell Depletion ◽  
Cytoskeletal Organization ◽  
Cell Localization ◽  
Fundamental Understanding ◽  
Injury And Repair ◽  
Fibril Diameter

AbstractDespite the requirement for Scleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLin cells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLin cells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTR mice would exhibit functionally deficient healing compared to wildtype littermates. Surprisingly, depletion of ScxLin cells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTR mice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLin cell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

scholarly journals Hypoxia-Induced Mesenchymal Stem Cells Exhibit Stronger Tenogenic Differentiation Capacities and Promote Patellar Tendon Repair in Rabbits

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Guanyin Chen ◽  
Wangqian Zhang ◽  
Kuo Zhang ◽  
Shuning Wang ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Patellar Tendon ◽  
Tendon Repair ◽  
Biomechanical Properties ◽  
Clinical Results ◽  
Medical Problem ◽  
Tendon Injury ◽  
Tenogenic Differentiation ◽  
Tgf Β1

Tendon injury is a common but tough medical problem. Unsatisfactory clinical results have been reported in tendon repair using mesenchymal stem cell (MSC) therapy, creating a need for a better strategy to induce MSCs to tenogenic differentiation. This study was designed to examine the effect of hypoxia on the tenogenic differentiation of different MSCs and their tenogenic differentiation capacities under hypoxia condition in vitro and to investigate the in vivo inductility of hypoxia in tenogenesis. Adipose tissue-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated and characterized. The expression of hypoxia-induced factor-1 alpha (Hif-1α) was examined to confirm the establishment of hypoxia condition. qRT-PCR, western blot, and immunofluorescence staining were used to evaluate the expression of tendon-associated marker Col-1a1, Col-3a1, Dcn, and Tnmd in AMSCs and BMSCs under hypoxia condition, compared with Tgf-β1 induction. In vivo, a patellar tendon injury model was established. Normoxic and hypoxic BMSCs were cultured and implanted. Histological, biomechanical, and transmission electron microscopy analyses were performed to assess the improved healing effect of hypoxic BMSCs on tendon injury. Our in vitro results showed that hypoxia remarkably increased the expression of Hif-1α and that hypoxia not only promoted a significant increase in tenogenic markers in both AMSCs and BMSCs compared with the normoxia group but also showed higher inductility compared with Tgf-β1. In addition, hypoxic BMSCs exhibited higher potential of tenogenic differentiation than hypoxic AMSCs. Our in vivo results demonstrated that hypoxic BMSCs possessed better histological and biomechanical properties than normoxic BMSCs, as evidenced by histological scores, patellar tendon biomechanical parameters, and the range and average of collagen fibril diameters. These findings suggested that hypoxia may be a practical and reliable strategy to induce tenogenic differentiation of BMSCs for tendon repair and could enhance the effectiveness of MSCs therapy in treating tendon injury.

Effect of rhPDGF-BB-Coated Sutures on Tendon Healing in a Rat Model: A Histological and Biomechanical Study

2011 ◽  
Author(s):  
S. Cummings ◽  
J. Dines ◽  
C. K. Hee ◽  
H. K. Kestler ◽  
C. M. Roden ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tissue Repair ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Biomechanical Study ◽  
Growth Factor Delivery ◽  
Delivery Method

Delivering growth factors to the site of injury using a coated suture delivery method has been investigated recently as a means to augment tissue repair [1]. This is a practical approach for growth factor delivery, as sutures are the method of choice for most orthopaedic surgeons for soft tissue repairs. One advantage of growth factor-coated sutures in tendon repair is the potential to accelerate healing in vivo, thereby improving the outcome of the repair. In particular, platelet-derived growth factor-BB (PDGF-BB) is a well characterized wound healing protein known to be chemotactic and mitogenic for cells of mesenchymal origin, including tenocytes, and has been shown to improve healing when applied to animal models of tendon injury [2,3]. The aim of this study was to compare the quality of the tendon repair at four weeks post treatment with sutures coated with varying concentrations of rhPDGF-BB, relative to buffer-coated suture repairs.

Pifithrin-α, an inhibitor of p53 transactivation, alters the inflammatory process and delays tendon healing following acute injury

2007 ◽  
Vol 292 (1) ◽  
pp. R321-R327 ◽  
Author(s):  
David Marsolais ◽  
Claude H. Côté ◽  
Jérôme Frenette
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Process ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Acute Injury ◽  
Inflammatory Phase ◽  
Load To Failure ◽  
Transcription Factor P53

Transcription factor p53, which was initially associated with cancer, has now emerged as an important regulator of inflammation and extracellular matrix homeostasis, two processes highly relevant to tendon repair. The goal of this study was to evaluate the effect of a p53 transactivation inhibitor, namely, pifithrin-α, on the pathophysiological sequence following collagenase-induced tendon injury. Administration of pifithrin-α during the inflammatory phase reduced the accumulation of neutrophils and macrophages by 30 and 40%, respectively, on day 3 postinjury. Pifithrin-α failed to reduce the percentage of apoptotic cells following collagenase injection but delayed functional recovery. In uninjured Achilles tendons, pifithrin-α increased metalloprotease activity 2.4-fold. Accordingly, pifithrin-α reduced the collagen content in intact tendons as well as in injured tendons 7 days posttrauma compared with placebo. The effect of pifithrin-α on load to failure and stiffness was also evaluated. The administration of pifithrin-α during the inflammatory phase did not significantly decrease the functional deficit 3 days posttrauma. More importantly, load to failure and stiffness were significantly decreased in the pifithrin-α group from day 7 to day 28 compared with placebo. Overall, our results suggest that administration of pifithrin-α alters the inflammatory process and delays tendon healing. The present findings also support the concept that p53 can regulate extracellular matrix homeostasis in vivo.

scholarly journals Interplay of Forces and the Immune Response for Functional Tendon Regeneration

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuwei Yang ◽  
Yicong Wu ◽  
Ke Zhou ◽  
Dongmei Wu ◽  
Xudong Yao ◽  
...  
Keyword(s):  
Immune Response ◽  
Tensile Strength ◽  
Tendon Healing ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Rapid Decline ◽  
Sports Activity ◽  
Tendon Regeneration ◽  
Functional Regeneration ◽  
External Forces

Tendon injury commonly occurs during sports activity, which may cause interruption or rapid decline in athletic career. Tensile strength, as one aspect of tendon biomechanical properties, is the main parameter of tendon function. Tendon injury will induce an immune response and cause the loss of tensile strength. Regulation of mechanical forces during tendon healing also changes immune response to improve regeneration. Here, the effects of internal/external forces and immune response on tendon regeneration are reviewed. The interaction between immune response and internal/external forces during tendon regeneration is critically examined and compared, in relation to other tissues. In conclusion, it is essential to maintain a fine balance between internal/external forces and immune response, to optimize tendon functional regeneration.

scholarly journals CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4

2021 ◽  
Vol 22 (18) ◽  
pp. 9729
Author(s):  
Neil Marr ◽  
Richard Meeson ◽  
Elizabeth F. Kelly ◽  
Yongxiang Fang ◽  
Mandy J. Peffers ◽  
...  
Keyword(s):  
Expression Patterns ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Focal Lesion ◽  
Post Injury ◽  
Surface Receptors ◽  
Basement Membrane Protein ◽  
Injury Model ◽  
Cell Niche

The interfascicular matrix (IFM) binds tendon fascicles and contains a population of morphologically distinct cells. However, the role of IFM-localised cell populations in tendon repair remains to be determined. The basement membrane protein laminin-α4 also localises to the IFM. Laminin-α4 is a ligand for several cell surface receptors, including CD146, a marker of pericyte and progenitor cells. We used a needle injury model in the rat Achilles tendon to test the hypothesis that the IFM is a niche for CD146+ cells that are mobilised in response to tendon damage. We also aimed to establish how expression patterns of circulating non-coding RNAs alter with tendon injury and identify potential RNA-based markers of tendon disease. The results demonstrate the formation of a focal lesion at the injury site, which increased in size and cellularity for up to 21 days post injury. In healthy tendon, CD146+ cells localised to the IFM, compared with injury, where CD146+ cells migrated towards the lesion at days 4 and 7, and populated the lesion 21 days post injury. This was accompanied by increased laminin-α4, suggesting that laminin-α4 facilitates CD146+ cell recruitment at injury sites. We also identified a panel of circulating microRNAs that are dysregulated with tendon injury. We propose that the IFM cell niche mediates the intrinsic response to injury, whereby an injury stimulus induces CD146+ cell migration. Further work is required to fully characterise CD146+ subpopulations within the IFM and establish their precise roles during tendon healing.

scholarly journals Mkx Mediates Tenogenic Differentiation But Incompletely Inhibits The Proliferation of Hypoxic MSCs

2021 ◽  
Author(s):  
Guanyin Chen ◽  
Dong Fan ◽  
Wangqian Zhang ◽  
Shuning Wang ◽  
Jintao Gu ◽  
...  
Keyword(s):  
Tendon Repair ◽  
Biomechanical Properties ◽  
Tendon Injury ◽  
Cell Counting ◽  
Differentiation Markers ◽  
Proliferation Capacity ◽  
Tenogenic Differentiation ◽  
Differentiation And Proliferation

Abstract Background: Hypoxia has been shown to be able to induce tenogenic differentiation of mesenchymal stem cells (MSCs) which lead hypoxia-induced MSCs to be a potential treatment for tendon injury. However, little is known about the mechanism underlying the tenogenic differentiation process of hypoxic MSCs, which limited the application of differentiation-inducing therapies in tendon repair. This study was designed to investigate the role of Mohawk homeobox (Mkx) in tenogenic differentiation and proliferation of hypoxic MSCs.Methods: Adipose-derived MSCs (AMSCs) and bone marrow-derived MSCs (BMSCs) were isolated, identified and cultured as our previous study. qRT-PCR, western blot, and immunofluorescence staining were performed to evaluate the expression of Mkx and other tendon-associated markers in AMSCs and BMSCs under hypoxia condition. Small interfering RNA technique was applied to observe the effect of Mkx levels on the expression of tendon-associated markers in normoxic and hypoxic BMSCs. Hypoxic BMSCs infected with Mkx-specific short hair RNA (shRNA) or scramble were implanted into the wound gaps of injured patellar tendons to assess the effect of Mkx levels on tendon repair. In addition, cell counting kit‑8 and colony formation unit assays were adopted to determine the proliferation capacity of normoxic or hypoxic BMSCs infected with or without Mkx-specific shRNA.Results: Our data showed that the expression of Mkx significantly increased in hypoxic AMSCs, and increased much more in hypoxic BMSCs. Our results also detected that the expression of tenogenic differentiation markers after down-regulation of Mkx were significantly decreased not only in normoxic BMSCs, but also in hypoxic BMSCs which paralleled the inferior histological evidences, worse biomechanical properties and smaller diameters of collagen fibrils in vivo. In addition, our in vitro data demonstrated that the optical density values and the clone numbers of both normoxic and hypoxic BMSCs were significantly increased after knockdown of Mkx, and were also significantly enhanced in both AMSCs and BMSCs in hypoxia condition under which the expression of Mkx was up-regulated.Conclusions: These findings strongly suggested that Mkx mediated hypoxia-induced tenogenic differentiation of MSCs, but could not completely repress the proliferation of hypoxic MSCs.

scholarly journals Basic Research on Tendon Repair: Strategies, Evaluation, and Development

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhi Jie Li ◽  
Qian Qian Yang ◽  
You Lang Zhou
Keyword(s):  
Wound Healing ◽  
Platelet Rich Plasma ◽  
Healing Process ◽  
Tendon Repair ◽  
Continuous Optimization ◽  
Tendon Healing ◽  
Basic Research ◽  
Clinical Problem ◽  
Tendon Injury ◽  
Wound Healing Process

Tendon is a fibro-elastic structure that links muscle and bone. Tendon injury can be divided into two types, chronic and acute. Each type of injury or degeneration can cause substantial pain and the loss of tendon function. The natural healing process of tendon injury is complex. According to the anatomical position of tendon tissue, the clinical results are different. The wound healing process includes three overlapping stages: wound healing, proliferation and tissue remodeling. Besides, the healing tendon also faces a high re-tear rate. Faced with the above difficulties, management of tendon injuries remains a clinical problem and needs to be solved urgently. In recent years, there are many new directions and advances in tendon healing. This review introduces tendon injury and sums up the development of tendon healing in recent years, including gene therapy, stem cell therapy, Platelet-rich plasma (PRP) therapy, growth factor and drug therapy and tissue engineering. Although most of these therapies have not yet developed to mature clinical application stage, with the repeated verification by researchers and continuous optimization of curative effect, that day will not be too far away.

Evaluation of a Novel Degradable Synthetic Biomaterial Patch for Augmentation of Tendon Healing in a Large Animal Model

2018 ◽  
Vol 32 (05) ◽  
pp. 434-440 ◽  
Author(s):  
Wayne Gersoff ◽  
Chantelle Bozynski ◽  
Cristi Cook ◽  
Ferris Pfeiffer ◽  
Keiichi Kuroki ◽  
...  
Keyword(s):  
Biomechanical Testing ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Standard Of Care ◽  
Tendon Injury ◽  
Large Animal Model ◽  
Large Animal ◽  
Range Of Movement ◽  
Limb Function ◽  
Group Outcomes

AbstractTendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.

Number of suture throws and its impact on the biomechanical properties of the four-strand cruciate locked flexor tendon repair with FiberWire

2012 ◽  
Vol 37 (9) ◽  
pp. 826-831 ◽  
Author(s):  
S. V. Le ◽  
S. Chiu ◽  
R. C. Meineke ◽  
P. Williams ◽  
M. D. Wongworawat
Keyword(s):  
Tensile Strength ◽  
Ultimate Tensile Strength ◽  
Flexor Tendon ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Early Mobilization ◽  
Biomechanical Properties ◽  
Optimal Number ◽  
Flexor Tendon Repair ◽  
Mode Of Failure

FiberWire is a popular suture in flexor tendon repair that allows for early mobilization, but its poor knot-holding properties have raised concerns over the potential effects on tendon healing and strength. We examined how the number of knot throws affects the 2 mm gap force, ultimate tensile strength, and mode of failure in a four-strand cruciate locked tendon repair in porcine flexor tendons in order to elucidate the optimal number of suture throws. There was no effect on the 2 mm gap force with increasing knot throws, but there was a significant increase in ultimate tensile strength. A minimum of six-knot throws prevents unravelling, whereas five out of 10 of repairs unravelled with less than six throws.

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